Serum Free Thyroid Hormone Levels Research Articles

Evaluation of an Association of Thyroid Disorder and Dyslipidemia in Patients with Cardiovascular Disease: A Cross-sectional Study

Background: Subclinical Hypothyroidism (SCH) is defined as normal serum free thyroid hormone levels coexisting with elevated serum Thyroid-Stimulating Hormone (TSH) levels. SCH is a common condition observed in clinical practice with several unique features. The present study was conducted to find prevalence of subclinical hypothyroidism in patients with myocardial infarction and demographic differences between patients with and without SCH. Materials and Methods: A total of 100 patients with Myocardial Infarction of Adult (age > 18 years) males and females were selected from the patients attending Medicine OPD, IPD or Intensive Care Unit (ICU) in GMC, Azamgarh. Clinical examination, laboratory investigations for myocardial infarction, thyroid status and lipid profile was done in all patients in our study. All Patients with TSH values > 10mU/L or < 0.04mU/L or Known cases of Thyroid abnormalities were excluded from the study. Statistical analysis was done using excel and SPSS software. Results: Out of 100 patients 44 patients of MI had subclinical hypothyroid were as rest 56 patients were euthyroid. In both the groups no statistical difference was seen in the type of Myocardial infarction. There was significant difference in lipid profile (p<0.05) in SCH group as compared to euthyroid group. Conclusion: Patients with Subclinical hypothyroid and MI had more lipid abnormalities as compared to Euthyroid group although the type of myocardial infarction was similar in both the groups. Males had more myocardial infarction as compared to females in both the subclinical hypothyroid and euthyroid groups.

Subclinical Hypothyroidism: Prevalence, Health Impact, and Treatment Landscape.

Subclinical hypothyroidism (sHypo) is defined as normal serum free thyroid hormone levels coexisting with elevated serum thyroid-stimulating hormone (TSH) levels. sHypo is a common condition observed in clinical practice with several unique features. Its diagnosis should be based on an understanding of geographic and demographic differences in biochemical criteria versus a global reference range for TSH that is based on the 95% confidence interval of a healthy population. During the differential diagnosis, it is important to remember that a considerable proportion of sHypo cases are transient and reversible in nature; the focus is better placed on persistent or progressive forms, which mainly result from chronic autoimmune thyroiditis. Despite significant evidence documenting the health impacts of sHypo, the effects of levothyroxine treatment (LT4-Tx) in patients with sHypo remains controversial, especially in patients with grade 1 sHypo and older adults. Existing evidence suggests that it is reasonable to refrain from immediate LT4-Tx in most patients if they are closely monitored, except in women who are pregnant or in progressive cases. Future research is needed to further characterize the risks and benefits of LT4-Tx in different patient cohorts.

Long-term physiological T3 supplementation in hypertensive heart disease in rats.

Animal studies suggest that hypertension leads to cardiac tissue hypothyroidism, a condition that can by itself lead to heart failure. We have previously shown that short-term thyroid hormone treatment in Spontaneously Hypertensive Heart Failure (SHHF) rats near heart failure is beneficial. This study tested the hypothesis that therapeutic, long-term T3 treatment in SHHF rats can prevent or attenuate cardiac dysfunction. Female SHHF rats were treated orally with a physiological T3 dose (0.04 μg/ml) from 12 to 24 mo of age. Age-matched female SHHF and Wistar-Kyoto rats served as hypertensive and normotensive controls, respectively. SHHF rats had reduced serum free thyroid hormone levels and cardiac tissue T3 levels, LV dysfunction, and elevated LV collagen content compared with normotensive controls. Restoration of serum and cardiac tissue thyroid hormone levels in T3-treated rats was associated with no change in heart rate, but strong trends for improvement in LV systolic function and collagen levels. For instance, end-systolic diameter, fractional shortening, systolic wall stress, and LV collagen levels were no longer significantly different from controls. In conclusion, longstanding hypertension in rats led to chronic low serum and cardiac tissue thyroid hormone levels. Long-term treatment with low-dose T3 was safe. While cardiac dysfunction could not be completely prevented in the absence of antihypertensive treatment, T3 may offer additional benefits as an adjunct therapy with possible improvement in diastolic function.

Aberrant Expression of Thyroid Hormone Receptor β Isoform May Cause Inappropriate Secretion of TSH in a TSH-Secreting Pituitary Adenoma

Patients with TSH-secreting pituitary adenomas (TSHoma) show inappropriate secretion of TSH; serum TSH levels are not suppressed despite high serum free thyroid hormone levels. The mechanism of a defect in negative regulation of TSH in a TSHoma is still unclear. Recently, we cloned a novel thyroid hormone receptor β isoform (TRβ4) from a human pituitary library. To elucidate the clinical significance of TRβ4, we investigated the expression of this isoform in TSHoma. RT-PCR was performed to detect TRβ isoforms such as TRβ1, TRβ2, and TRβ4 using RNA obtained from surgically resected TSHoma. The effects of TRβ4 on the TSH gene expression were examined in the transient gene expression experiments. Quantitative analysis using a real-time PCR revealed that relative expression of TRβ4 to TRβ1+2 was higher in three TSHoma than in a prolactinoma or a nonfunctioning pituitary adenoma. TRβ4 construct did not mediate T(3)-dependent gene regulation but inhibited the negative regulation of TSHα mediated by TRβ1 or TRβ2. Aberrant expression of TRβ4 may partly contribute to the inappropriate secretion of TSH in a TSHoma.

Plasma total and acylated Ghrelin concentrations in patients with clinical and subclinical thyroid dysfunction

Results of circulating Ghrelin levels in hyper- or hypothyroidism are conflicting and only overt thyroid dysfunction has been evaluated. To evaluate in a large number of patients with thyroid disfunction whether: a) hyper- and hypothyroidism (clinical or subclinical) are associated with variations in both acylated (AG) and total Ghrelin (TG) concentrations, and b) correction of thyroid dysfunction is followed by variations in Ghrelin concentrations. Seventy-six hyperthyroids, 52 hypothyroids, 144 euthyroids with chronic autoimmune thyroiditis, and 109 euthyroid healthy controls were evaluated cross-sectionally and longitudinally. TG and AG were significantly lower in hyperthyroids than in controls or hypothyroids; the latter 2 groups did not differ. TG was significantly lower in overt than in subclinical hyperthyroids, with a trend to a reduction also in AG levels. No differences were found between subclinical hyperthyroids and controls. After thionamide treatment, TG and AG levels in hyperthyroids did not differ from controls. L-thyroxine management of hypothyroidism was not associated with significant Ghrelin variations. Plasma Ghrelin was independent of either thyroid or gastric autoimmunity. Plasma TG was negatively correlated with serum free thyroid hormone levels in hyperthyroids but not in hypothyroids. Plasma Ghrelin concentrations are reduced in overt but not in subclinical hyperthyroidism and normalize after restoration of euthyroidism. Hypothyroidism is not accompanied by significant changes in circulating Ghrelin.

Asymptomatic Hyperthyroidism in Older Adults

Hyperthyroidism is the result of increased serum free thyroid hormone levels and is associated with a well recognized set of clinical signs and symptoms. However, older patients who develop hyperthyroidism tend to have fewer hyperadrenergic signs and an increased incidence of weight loss, cardiac arrhythmias and, occasionally, apathetic mood. This article highlights the paucity of clinical signs and symptoms of hyperthyroidism in older people and reviews the potential biochemical changes in thyroid hormone physiology that may account for an altered clinical presentation in older people with hyperthyroidism. First, a brief vignette from our own clinical practice is described to highlight an unusual presentation of hyperthyroidism in an older woman. The subject is then reviewed on the basis of relevant articles identified through a MEDLINE search of the English literature, using the key words 'hyperthyroidism' and 'aging'. The available evidence indicates that the clinical syndrome of asymptomatic hyperthyroidism in older adults appears to be distinct from the more widely recognized syndromes of apathetic hyperthyroidism or thyroid hormone resistance. Age-related changes in thyroid hormone economy and reduced cellular uptake of thyroid hormone as well as changes in thyroid hormone regulation of gene expression may account for reduced manifestations of hyperthyroidism in older adults. Thus, in addition to the well known changes in thyroid gland anatomy and function with aging, there may be an age-related resistance to thyroid hormone action. Asymptomatic hyperthyroidism may well be a syndrome that is currently under-diagnosed.

The association between subclinical hyperthyroidism and blood pressure in a population-based study

Although evidence for an increased risk of hypertension in both overt hyperthyroidism and overt hypothyroidism is consistent, the relation between subclinical hyperthyroidism and blood pressure has not yet received sufficient attention. The Study of Health in Pomerania is a population-based survey in Germany that was conducted in a previously iodine-deficient region. A study population of 4087 subjects (2050 women) without overt hyperthyroidism or increased serum thyrotropin levels was available for the present study. Serum thyrotropin levels < 0.25 mIU/l and < 0.1 mIU/l were considered decreased and suppressed, respectively. Multivariable analyses revealed lower adjusted mean values for systolic blood pressure in subjects with decreased [132.9 mmHg, 95% confidence interval (CI) = 131.1 mmHg; 134.8 mmHg] versus normal serum thyrotropin levels (135.0 mmHg, 95% CI = 134.4 mmHg; 135.6 mmHg, P = 0.04). The adjusted mean values for diastolic blood pressure and pulse pressure did not differ significantly between both groups. Analyses that were performed after all subjects receiving antihypertensive medications had been excluded did not reveal any statistically significant associations between decreased serum thyrotropin levels and the endpoints investigated. There was also no association of suppressed serum thyrotropin levels with blood pressure or hypertension. It is concluded that subclinical hyperthyroidism, as demonstrated by decreased as well as suppressed serum thyrotropin levels and serum free thyroid hormone levels within the reference range, is not associated with hypertension.

Treatment for Congenital Hypothyroidism: Thyroxine Alone or Thyroxine Plus Triiodothyronine?

To compare the effects of therapy with thyroxine (T4) plus triiodothyronine (T3) versus T4 alone from the first days of life in screened congenital hypothyroid (CH) infants. We examined 14 CH infants diagnosed by neonatal screening and a group of control infants. CH patients were divided randomly into 2 groups, 1 treated with T4 alone (group 1) and the other treated with T4 plus T3 (liothyronine; group 2). In all patients electrocardiography and thyroid hormone evaluations were performed before and 15 and 30 days and 3, 6, and 12 months after the beginning of therapy. Psychological tests were also performed at 6 and 12 months of age in CH patients and in other matched controls. After 15 days of treatment, serum thyrotropin (TSH) levels become normal in 5 of 7 cases of group 1 (median TSH level 10.7 micro U/ml) and in 1 of 7 cases of group 2 (median TSH level 72.5 micro U/ml). At the same period, serum-free thyroid hormone levels were within the normal range in both groups, but free T4 values were significantly higher in group 1 than in group 2 and in controls. At the subsequent examinations, free T4 values were within the upper normal limit in group 1, whereas they remained within the normal range in group 2. No clinical or electrocardiographic signs of heart disease were found in any of the patients. The psychometric quotient in CH infants was significantly lower than in controls, but similar in patients of group 1 and group 2. The combined treatment with T4 plus T3 seems not to show significant advantages, at least in our experimental conditions, compared with the traditional treatment with T4 alone in early treated CH infants. A further longer and more extensive follow-up is mandatory.

The Nocturnal Serum Thyrotropin Surge Is Inhibited in Patients with Adrenal Incidentaloma

BackgroundAlterations in hypothalamic-pituitary function have been described in patients with incidentally discovered adrenal adenomas and have been attributed to their subtle hypercortisolemic status.MethodsTo establish whether the central control of the...

Drug therapy for hyperthyroidism in pregnancy: safety issues for mother and fetus.

Hyperthyroidism (thyrotoxicosis) in pregnancy and the child bearing years is usually attributable to Graves' disease. This is an autoimmune condition in which thyroid-stimulating immunoglobulins (TSI) cause hyperthyroidism. As a rule, pregnancy complicates the management of hyperthyroidism, rather than vice versa. However, patients who remain thyrotoxic during pregnancy are at increased risk of maternal and fetal complications, particularly miscarriage and stillbirth. Therefore, bodyweight loss, eye signs and a bruit over the thyroid gland in a pregnant woman warrant thyroid investigation. Investigations should include measurement of serum free thyroid hormone levels [free thyroxine (T4) and free triiodothyronine (T3)] rather than total T4 and T3 levels, because total T4 and T3 levels may be raised in euthyroid pregnancies due to the presence of increased levels of thyroxine binding globulin (TBG). By 20 weeks' gestational age, the fetal thyroid is fully responsive to TSI and to antithyroid drugs. Maternal T4 and T3 and thyrotropin pass across the placenta in small and decreasing amounts as gestation progresses, but thyrotropin releasing hormone, TSI, antithyroid drugs, iodides and beta-blockers are readily transferred to the fetus from the mother. Hyperthyroidism is usually treated throughout pregnancy with an antithyroid drug, preferably propylthiouracil. The smallest dose which controls the disease is given with careful monitoring of free T4 and T3 levels to minimise the risk of fetal hypothyroidism and goitre. Bilateral subtotal thyroidectomy may be an option for a small number of patients with hyperthyroidism in pregnancy.

Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone.

Steroid receptor co-activator 1 (SRC-1) is a transcription co-factor that enhances the hormone-dependent action, mediated by the thyroid hormone (TH) receptor (TR) and other nuclear receptors. In vitro studies have shown that SRC-1 is necessary for the full expression of TH effect. SRC-1 knockout mice (SRC-1(-/-)) provide a model to examine the role of this co-activator on TH action in vivo. At baseline, SRC-1(-/-) mice display resistance to TH (RTH) as evidenced by a 2.5-fold elevation of serum TSH levels, despite a 50% increase in serum free TH levels as compared with wild-type (SRC-1(+/+)) mice. When mice were made hypothyroid, TSH levels increased, obliterating the difference between SRC-1(+/+) and SRC-1(-/-) mice observed at baseline. In contrast, the decline of TSH by treatment with L-triiodothyronine was severely blunted in SRC-1(-/-) mice. These data indicate that SRC-1 is not required for the upregulation of TSH in TH deficiency. However, SRC-1 enhances the sensitivity of TSH downregulation by TH. This is the first demonstration of RTH caused by a deficient co-factor other than TR. It supports the hypothesis that a putative defect in the SRC-1 gene or another co-factor could be the cause of RTH in humans without mutations in the TR genes.

Influence of residual C-peptide secretion on nocturnal serum TSH peak in well-controlled diabetic patients.

Several alterations in hypothalamo-pituitary-thyroid (HPT) function have been described in diabetes mellitus and have been attributed to metabolic decompensation. The present study was performed in order to establish whether residual endogenous insulin secretion in patients with insulin-dependent diabetes mellitus (IDDM) may play a role in the control of HPT function. The nocturnal (2230 h-0200 h) serum TSH surge, the TSH response to TRH (200 microgram as an i.v. bolus) and serum free thyroid hormone levels were evaluated in C-peptide positive (CpP) (subjects with residual detectable endogenous pancreatic beta-cell activity) and C-peptide negative (CpN) patients both before and after optimization of metabolic status by 3 days of treatment with continuous subcutaneous insulin infusion, and in normal controls. TSH response to TRH and serum free thyroid hormone levels were assessed in the morning. Twenty male diabetic patients hospitalized to achieve a better control of hyperglycaemia were subdivided into 10 CpP (age: 33 +/- 1.5 years (mean +/- SE); body mass index (BMI): 22.6 +/- 0.3) and 10 CpN (age: 32 +/- 1.7 years; BMI: 22.5 +/- 0.4) patients. Nine normal men (age: 34.0 +/- 1.2 years; BMI: 23.1 +/- 0.4) served as controls. The nocturnal serum TSH peak was measured by dividing the highest night-time TSH value by the next morning TSH value and then multiplying by 100. Serum TSH levels were measured in samples taken just before (time 0) and 30 minutes, after TRH administration. Serum free thyroid hormone levels were measured in samples taken at time 0 of the TRH test. Before improvement of hyperglycaemia, CpP and CPN patients showed similar alterations in HPT function; i.e. serum free T3 levels and TSH responses to TRH were lower than normal; the nocturnal TSH surge was absent. Correction of hyperglycaemia normalized all examined HPT parameters in CpP diabetics, whereas normalization in serum free T3 levels and pituitary TSH responsiveness to TRH in CpN patients was not accompanied by restoration of the nocturnal TSH peak. These data indicate that the absence of residual pancreatic beta-cell function in patients with insulin-dependent diabetes mellitus is associated with neuroendocrine dysfunction in the regulation of circadian TSH secretion, which is not reversible after restoration of good glycaemic control.

Elevated plasma adrenomedullin level in hyperthyroidism.

Adrenomedullin is a recently discovered peptide that was first purified from phaeochromocytoma tissue and has marked vasodilatory activity, causing hypotension. In thyrotoxicosis, various haemodynamic changes are observed, including an increase in cardiac output and heart rate with a concomitant decrease in peripheral vascular resistance. To evaluate the mechanism underlying these haemodynamic changes in thyrotoxicosis, we measured the plasma adrenomedullin concentration in thyrotoxic patients with Graves' disease. The plasma concentration of adrenomedullin was elevated in hyperthyroid patients (14.7 +/- 5.7 pmol L-1) compared with euthyroid control subjects (5.6 +/- 1.3 pmol L-1) (P < 0.001). The correlation between the plasma adrenomedullin concentration and serum free thyroid hormone levels was marginally significant. The mean blood pressure was relatively low in the face of an elevated plasma adrenomedullin level. Adrenomedullin may therefore be responsible for the vasodilatation observed in thyrotoxicosis.

Lack of seasonal variation in abnormal TSH secretion in patients with seasonal affective disorder

The circadian variations in thyroid-stimulating hormone (TSH) secretion, with particular attention to the nocturnal serum TSH surge and the TSH response to thyrotropin releasing hormone (TRH), were measured in seven patients with seasonal affective disorder (SAD) and in eight normal controls. Both patients with SAD and normal controls were tested in fall/winter, when patients were suffering depressive symptoms, and in spring/summer, when patients were euthymic. The TRH tests were performed in the morning. In all tests, the mean peak TSH response to TRH was significantly lower in the patients with SAD than in the normal controls. No significant differences were observed in either group between spring/summer and fall/winter tests. At both periods, patients with SAD showed normal TSH levels in the morning, but did not experience a nocturnal TSH surge. In this group, morning and night TSH levels were similar. In contrast, normal controls showed significantly higher TSH levels at night than in the morning. Serum-free thyroid hormone levels were in the normal range in all subjects. Morning and night serum cortisol levels and 24-hour urinary cortisol concentrations were similar in all subjects. These data show that the secretion of TSH is impaired in SAD, regardless of the phase of the psychiatric disease. The low TSH response to TRH in the presence of normal serum thyroid hormone levels and the lack of the TSH nocturnal surge suggest that patients with SAD might be affected by mild central hypothyroidism.

Correlations between grasp-reflex strengths and serum thyroid-hormone levels depending upon sex and familial sinistrality in human neonates: importance of genetically predetermined cerebral organization.

Relations of grasp-reflex strengths to serum free-thyroid hormone levels were studied in human neonates. In right-dominant (RH) males and females without familial sinistrality (-FS), grasp-reflex strengths from right (R) and left (L) inversely correlated with serum triiodothyronine (T3). In RH, +FS males, grasp-reflex strengths from R and L hands directly correlated with T3 (no correlations in RH, +FS females). There was no significant correlation between grasp reflex and T3 in non-right-handed (NRH), -FS neonates. In NRH +FS neonates, there was a significant negative linear correlation between grasp reflex from left and T3 only in NRH, +FS males. The following correlations were found between grasp reflex and thyroxine (T4): direct relation in RH, +FS males and females; inverse relation in NRH, -FS females only for the right hand; inverse correlations in NRH, +FS females. The R-L grasp reflex directly correlated with T3 in RH, -FS males, and inversely correlated with T3 in RH, -FS females (no significant correlations in others). These results indicated that thyroid hormones may influence cerebral maturation and lateralization differentially according to genetically predetermined cerebral organization. The generalizations of the hormonal effects on, at least, cerebral functioning would be wrong, if the genetically predetermined main features of the brain are neglected.

Percutaneous intranodular ethanol injection: A new treatment for autonomous thyroid adenoma

Established methods for definitive ablation of autonomous thyroid nodules are surgery and radioiodine. Since it has been demonstrated that percutaneous ethanol injection can inactivate parathyroid adenomas and small hepatocellular carcinomas, we started a trial of this treatment in patients with autonomous thyroid nodules. Twenty-eight patients, 22 toxic and 6 nontoxic, all with undetectable thyrotropin serum levels and suppressed extranodular tissue on scintigraphy, were treated. Treatment consisted of percutaneous intranodular ethanol injection under ultrasound guidance. The total amount of alcohol injected ranged from 0.4 to 2.2 times the estimated nodule volume, divided into 4 to 9 injections performed at 2 to 7 day intervals. Most patients were treated with a single cycle of injections, but 7 of them required 2 cycles. The signs and symptoms of hyperthyroidism disappeared in all cases. Apparently complete cure (normal serum free thyroid hormones, thyrotropin in basal conditions and after thyrotropin releasing hormone, reactivation of extranodular tissue on scintigraphy with nodule no longer visible) was obtained in 17 patients (13 after 1 cycle and 4 after 2 cycles). Partial cure (normal serum free thyroid hormone levels, detectable thyrotropin levels with normal or blunted response to thyrotropin releasing hormone and partial reactivation of extranodular tissue on scintigraphy with nodule or parts of it still visible) was obtained in 10 patients (8 after 1 cycle and 2 after 2 cycles). In 1 patient with a very large nodule thyrotropin levels remained undetectable, but thyroid hormone levels eventually became normal. No recurrences were observed after a follow-up of 12 to 32 months (mean 20 months). No serious side effects were encountered. A clinically valuable result was obtained in all patients. These data suggest that this form of treatment could constitute an alternative to surgery and radioiodine for the ablation of autonomous thyroid nodules.